osteoporosis is the most common endemic disease on the rise.if not diagnosed early,it may lead to many complications.

2. Pathogenesis of osteoporosis

3. Definition:
Metabolic bone disease categorized by histology :
Osteoporosis Osteomalacia
Decrease in matrix Bone matrix intact
and mineral. reduced mineral.
Osteoporosis defintion by NIH Consensus
Conference, 2000: Skeletal disorder characterized by compromised
bone strength predisposing to an increased risk of fracture.
Bone strength= Bone density + Bone quality1

4. Regulation of bone remodeling.
Signals that determine the
differentiation, function, and
death of these cells and their
progenitors determine how many
units are activated over time,
how active and well-balanced
the basic multicellular unit is,
and whether, at the end of the
cycle, bone mass will be gained,
lost, or stable4
Canalis E et al. N Engl J Med
2007;357:905-916

6. Systemic hormones involved:
• Parathyroid hormone - is the most important regulator of calcium homeostasis. It maintains serum
calcium concentrations by:
 Stimulating bone resorption
 Increasing renal tubular calcium reabsorption
 Increasing renal calcitriol production.
PTH stimulates bone formation when given intermittently, but inhibits collagen synthesis at high
concentrations 26,27. It stimulates osteoclast mediated bone resorption when given (or secreted)
continuously. It also stimulates gene expression and increases the production of several local factors,
including IL-6, IGF-1 and an IGF-binding protein, IGF-BP-5, and prostaglandins. 28,37.
Canalis E et al. N Engl J Med 2007;357:905-916

8.  Calcitriol : increases intestinal calcium and phosphorus absorption, thereby promoting bone
mineralization. At high concentrations, under conditions of calcium and phosphate deficiency, it
also stimulates bone resorption, thereby helping to maintain the supply of these ions to other
tissues.
 Calcitonin : inhibits osteoclasts and therefore bone resorption in pharmacologic doses. However,
its physiologic role is minimal in the adult skeleton. Its effects are transient, probably because of
receptor downregulation.
 Growth hormone and IGFs : The GH/IGF-1 system and IGF-2 are important for skeletal
growth, especially growth at the cartilaginous end plates and endochondral bone formation.

10. Osteoporotic bone showing loss of bone with larger spaces
decreasing its strength .2

12. Clinical risk factors:
Ebeling P. N Engl J Med 2008;358:1474-1482

14. BMD measurement:
1. Dual-Energy X-Ray Absorptiometry:
Results expressed as
• T-SCORE is the number of SD the measurement
is above or below the YOUNG-NORMAL MEAN
BMD.
• Z-SCORE is the number of SD the measurement
is above or below the AGE-MATCHED MEAN BMD.
Sites used for measurement per WHO criteria:
•Total proximal femur
•Femoral neck
•Lumbar spine
•33percent(1/3rd)radius if e/o OA or surgery at
other 3 sites.
Peripheral skeletal sites predict global #
risk, however not used in WHO/FRAX criteria
therefore limited value. Changes to therapy at
Raisz L. N Engl J Med 2005;353:164-171 these sites are slow.

16. WHO diagnostic categories of BMD
Ebeling P. N Engl J Med 2008;358:1474-1482

18. Other lab tests:
 Initial laboratory tests :
• Complete chemistry profile (including alkaline phosphatase)
• CBC
• Calcium, phosphorus
• 25 hydroxyvitamin D
• Urinary calcium excretion
 Additional laboratory tests if indicated(clinical features/ low Z-score)
• 24 hour urine for free cortisol
• Estradiol, FSH, LH, Prolactin , TSH
• Magnesium
• 1,25 dihydroxyvitamin D ,Intact PTH
• Celiac screen
• SPEP/UPEP
• ESR, Rheumatoid Factor
• Serum tryptase and histamine levels
• Homocysteine
• Skin biopsy for connective tissue disorders
• COL1A genetic testing for osteogenesis imperfecta
• Serum and urine markers of bone turnover

20. Thank You.

25. IN THE INTESTINE
It facilitates intestinal absorption of calcium, as
well as stimulates absorption of phosphate and
magnesium ions.
In the absence of vitamin D, dietary calcium is not
absorbed at all efficiently.
Vitamin D stimulates the expression of a number
of proteins involved in transporting calcium from
the lumen of the intestine, across the epithelial
cells and into blood.

27. The vitamin D form, 1,25-dihydroxcholecalciferol
[1,25(OH)2D3],
• 1. stimulates the synthesis of the epithelial calcium
channels in the plasma membrane calcium pumps , and
• 2. induces the formation of the calbindins.

29. Calcitriol Raises Blood
Calcium in 3 Ways:
1. Increases Ca++
absorption by the small
intestine.
2. Increases Calcium (and
Phosphate ) resorption
from the skeleton. It
binds to hematopoietic
stem cells and causes
differentiation of
osteoclasts.
3. Weakly promotes the
reabsorption of Calcium
ions by the kidney cells
(less calcium excreted)

31. Vitamin D has also been shown to play an
important part in regulating the proliferation
and differentiation of both types of
bone remodeling cells - those
responsible for bone breakdown and
those that reform the bone anew…and
more.
•

33. Parathyroid Gland Anatomy
• Four Parathyroid
glands are usually
found posterior to the
thyroid gland
• Total weight of
parathyroid tissue is
about 150mg
• Parathyroid hormone
(PTH) is made by these
glands

35. Low Blood Calcium
Parathyroid gland releases parathyroid hormone
Stimulates osteoclasts to resorb Ca++
Blood calcium rises
Promotes the final step of Calcitriol synthesis by
kidneys
Feedback Inhibition
High Blood Calcium
Inhibits parathyroid gland